ALG13-Congenital Disorder of Glycosylation (CDG), is a rare X-linked CDG caused by pathogenic variants in ALG13 (OMIM 300776) that affects the N-linked glycosylation pathway. Affected individuals present with a predominantly neurological manifestation during infancy. Epileptic spasms are a common presenting symptom of ALG13-CDG. Other common phenotypes include developmental delay, seizures, intellectual disability, microcephaly, and hypotonia. Current management of ALG13-CDG is targeted to address patients\' symptoms. To date, less than 100 individuals have been reported with ALG13-CDG. In this article, an international group of experts in CDG reviewed all reported individuals affected with ALG13-CDG and suggested diagnostic and management guidelines for ALG13-CDG. The guidelines are based on the best available data and expert opinion. Neurological symptoms dominate the phenotype of ALG13-CDG where epileptic spasm is confirmed to be the most common presenting symptom of ALG13-CDG in association with hypotonia and developmental delay. We propose that ACTH/prednisolone treatment should be trialed first, followed by vigabatrin, however ketogenic diet has been shown to have promising results in ALG13-CDG. In order to optimize medical management, we also suggest early cardiac, gastrointestinal, skeletal, and behavioral assessments in affected patients.

Corticosteroids have been used for the treatment of patients with epilepsy for more than 6 decades, based on the hypothesis of inflammation in the genesis and/or promotion of epilepsy. We, therefore, aimed to provide a systematic overview of the use of corticosteroid regimes in childhood epilepsies in line with the PRISMA guidelines. We performed a structured literature search via PubMed and identified 160 papers with only three randomized controlled trials excluding the substantial trials on epileptic spasms. Corticosteroid regimes, duration of treatment (days to several months), and dosage protocols were highly variable in these studies. Evidence supports the use of steroids in epileptic spasms; however, there is only limited evidence for a positive effect for other epilepsy syndromes, e.g., epileptic encephalopathy with spike-and-wave activity in sleep [(D)EE-SWAS] or drug-resistant epilepsies (DREs). In (D)EE-SWAS (nine studies, 126 patients), 64% of patients showed an improvement either in the EEG or in their language/cognition following various steroid treatment regimes. In DRE (15 studies, 436 patients), a positive effect with a seizure reduction in 50% of pediatric and adult patients and seizure freedom in 15% was identified; however, no recommendation can be drawn due to the heterozygous cohort. This review highlights the immense need for controlled studies using steroids, especially in DRE, to offer patients new treatment options.

Objective: Although vigabatrin (VGB) is effective and well tolerated for the treatment of epileptic spasms, there are safety concerns. The aim of this systematic review and metaanalysis was to assess adverse events of VGB for the treatment of epileptic spasms. Methods: MEDLINE, EMBASE, and Cochrane databases were searched. The population was infants treated with VGB for epileptic spasms. The outcomes were VGB-related adverse events. Meta-analyses of VGB-related MRI abnormalities, retinal toxicity as measured by electroretinogram (ERG), visual field defect as measured by perimetry, and other adverse events were conducted. Results: Fifty-seven articles were included in the systematic review. The rate of VGB-related MRI abnormalities was 21% (95% CI: 15-29%). Risk factors for MRI abnormalities were age younger than 12 months and higher VGB dose. VGB-related retinal toxicity and visual field defect occurred in 29% (95% CI: 7-69%) and 28% (95% CI: 4-78%) respectively. Other adverse events occurred in 23% (95% CI: 16-34%), consisting predominantly of central nervous system symptoms, and the majority of these did not require therapeutic modification. Conclusion: This study will inform physicians and families on the risk profile of VGB for the treatment of epileptic spasms and will help decisions on treatment options.